Studies carried out in our laboratory with the direct-acting chemical agents bis(chloromethyl)ether (BCME), dimethylcarbamoyl chloride, (DMCC), and epichlorohydrin (ECH) have shown that for these compounds, there is a direct, positive relationship between chemical reactivity, expressed as hydrolysis half time, and carcinogenic potency in the respiratory tract of the Sprague Dawley rat. If this relationship can be shown to hold for a wide range of direct-acting compounds, then the hydrolysis half time of a given compound would be a very useful criterion on which to make an initial determination of potential carcinogenic risk. The present studies will further test the hypothesis that chemical reactivity is an indicator of inhalation carcinogenic potency for direct-acting compounds by examining six additional compounds having a wide range of chemical reactivities-dichloroacetyl chloride (DCAC), beta-propiolactone (BPL), methyl fluorosulfonate (MFS), methyl methanesulfonate (MMS), ethyl chloroformate (ECF), and propylene oxide (PO). These compounds will be tested for carcinogenic potential by inhalation exposure of Sprague Dawley rats. All of the above agents will also be examined in vitro in the V79 mammalian cell mutagenesis system and in the C3H 10Tl/2 cell transformation system.